Matrix metalloproteinase-11/stromelysin-3 exhibits collagenolytic function against collagen VI under normal and malignant conditions

Er, Motrescu; Blaise, Sébastien; Etique, Nicolas; Messaddeq, Nadia; Chenard, M.P.; Stoll, Isabelle; Tomasetto, Catherine; Rio, Marc

doi:10.1038/onc.2008.218

Cited by 100 publications

(68 citation statements)

References 30 publications

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“…MMP-11 is required for correct collagen VI folding and therefore for fat tissue cohesion and adipocyte function. 46 Indeed, specific proteolysis is sometimes required for correct collagen formation/folding 47 . 48 Irrespective of the mechanism, by modulating pericellular collagen composition, MMP-11 regulates matrix stiffness and can thereby influence epithelial cell behavior, as previously reported.…”

Section: Discussionmentioning

confidence: 99%

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development

et al. 2013

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MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11 À / À ) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11 À / À cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11 À / À epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy.

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Section: Discussionmentioning

confidence: 99%

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development

et al. 2013

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“…It is a stromal mediator of cancer progression (8 ) that regulates the release of angiogenic factors and metastatic dissemination in experimental models (29 ). In breast cancer, MMP11 derived from cancer-associated adipocytes or fibroblastic cells exerts type VI collagenolytic activity (40 ). More recently, MMP2 has been shown to influence lymphangiogenesis through its interstitial collagenolytic activity (30 ).…”

Section: Ecm Remodelingmentioning

confidence: 99%

Targeting the Tumor Microenvironment for Cancer Therapy

2013

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BACKGROUND With the emergence of the tumor microenvironment as an essential ingredient of cancer malignancy, therapies targeting the host compartment of tumors have begun to be designed and applied in the clinic. CONTENT The malignant features of cancer cells cannot be manifested without an important interplay between cancer cells and their local environment. The tumor infiltrate composed of immune cells, angiogenic vascular cells, lymphatic endothelial cells, and cancer-associated fibroblastic cells contributes actively to cancer progression. The ability to change these surroundings is an important property by which tumor cells are able to acquire some of the hallmark functions necessary for tumor growth and metastatic dissemination. Thus in the clinical setting the targeting of the tumor microenvironment to encapsulate or destroy cancer cells in their local environment has become mandatory. The variety of stromal cells, the complexity of the molecular components of the tumor stroma, and the similarity with normal tissue present huge challenges for therapies targeting the tumor microenvironment. These issues and their interplay are addressed in this review. After a decade of intensive clinical trials targeting cellular components of the tumor microenvironment, more recent investigations have shed light on the important role in cancer progression played by the noncellular stromal compartment composed of the extracellular matrix. SUMMARY A better understanding of how the tumor environment affects cancer progression should provide new targets for the isolation and destruction of cancer cells via interference with the complex crosstalk established between cancer cells, host cells, and their surrounding extracellular matrix.

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“…Further, MMP-11 has a weak caseinolytic activity and it has been shown to cleave insulin-like growth factor-binding protein-1 (IGF-BP-1) in a carcinoma cell line (Pei et al, 1994). Recent research has demonstrated that, although MMP-11 does not cleave many ECM proteins, degradation of type VI collagen could be physiologically related to adipogenesis inhibition (Motrescu et al, 2008).…”

Section: Structural Peculiarities and Biological Aspectsmentioning

confidence: 99%

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

Sbardella

Fasciglione

Gioia

et al. 2012

Molecular Aspects of Medicine

205

212

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a b s t r a c tHuman matrix metalloproteinases (MMPs) belong to the M10 family of the MA clan of endopeptidases. They are ubiquitarian enzymes, structurally characterized by an active site where a Zn 2+ atom, coordinated by three histidines, plays the catalytic role, assisted by a glutamic acid as a general base. Various MMPs display different domain composition, which is very important for macromolecular substrates recognition. Substrate specificity is very different among MMPs, being often associated to their cellular compartmentalization and/or cellular type where they are expressed. An extensive review of the different MMPs structural and functional features is integrated with their pathological role in several types of diseases, spanning from cancer to cardiovascular diseases and to neurodegeneration. It emerges a very complex and crucial role played by these enzymes in many physiological and pathological processes.

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Matrix metalloproteinase-11/stromelysin-3 exhibits collagenolytic function against collagen VI under normal and malignant conditions

Cited by 100 publications

References 30 publications

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development

Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development

Targeting the Tumor Microenvironment for Cancer Therapy

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

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